A protective antigen mutation increases the pH threshold of anthrax toxin receptor 2-mediated pore formation.
A protective antigen mutation increases the pH threshold of anthrax toxin receptor 2-mediated pore formation.
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保护性抗原突变增加了炭疽毒素受体2介导的孔形成的pH阈值。
DOI：
10.1021/bi5000756
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发表时间：
2014-04-08
期刊：
影响因子：
2.9
通讯作者：
Mogridge J
中科院分区：
文献类型：
--
作者：
Dennis MK;Mogridge J
炭疽毒素保护性抗原（PA）结合细胞受体并自组装成寡聚前孔。前孔在其已被运输到内体之后转化为蛋白质易位孔，在内体中低pH触发跨膜β-桶通道的形成。该通道的形成发生在一些PA-受体接触被破坏以允许孔形成之后，而另一些则被保留以保持受体缔合。PA与炭疽毒素受体1（ANTXR 1）之间的相互作用弱于其与ANTXR 2的相互作用，使得ANTXR 1介导的孔形成的pH阈值高1个pH单位。在这里，我们研究受体特异性的毒素结合和孔形成的差异突变PA残基G342选择性邻接ANTXR 2。G342突变为缬氨酸、亮氨酸、异亮氨酸或色氨酸增加了与表达ANTXR 1的细胞结合的PA的量，降低了与表达ANTXR 2的细胞结合的PA的量。更保守的G342 A突变不影响与ANTXR 2的结合水平，但ANTXR 2结合的PA-G342 A前孔表现出比野生型前孔更高的pH阈值。野生型PA和PA-G342 A的混合物在毒性测定中是功能性的，并且ANTXR 2介导的孔形成的pH阈值由异源寡聚体中两种蛋白质的相对量决定。这些结果表明，PA亚基内的寡聚体不必须同时触发生产性膜插入事件发生。
Anthrax toxin protective antigen (PA) binds cellular receptors and self-assembles into oligomeric prepores. A prepore converts to a protein translocating pore after it has been transported to an endosome where the low pH triggers formation of a membrane-spanning β-barrel channel. Formation of this channel occurs after some PA–receptor contacts are broken to allow pore formation, while others are retained to preserve receptor association. The interaction between PA and anthrax toxin receptor 1 (ANTXR1) is weaker than its interaction with ANTXR2 such that the pH threshold of ANTXR1-mediated pore formation is higher by 1 pH unit. Here we examine receptor-specific differences in toxin binding and pore formation by mutating PA residue G342 that selectively abuts ANTXR2. Mutation of G342 to valine, leucine, isoleucine, or tryptophan increased the amount of PA bound to ANTXR1-expressing cells and decreased the amount of PA bound to ANTXR2-expressing cells. The more conservative G342A mutation did not affect the level of binding to ANTXR2, but ANTXR2-bound PA-G342A prepores exhibited a pH threshold higher than that of wild-type prepores. Mixtures of wild-type PA and PA-G342A were functional in toxicity assays, and the pH threshold of ANTXR2-mediated pore formation was dictated by the relative amounts of the two proteins in the hetero-oligomers. These results suggest that PA subunits within an oligomer do not have to be triggered simultaneously for a productive membrane insertion event to occur.
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影响因子：
16.8
作者：
通讯作者：
--
DOI：
10.1073/pnas.0431098100
发表时间：
2003-04-29
影响因子：
11.1
作者：
Scobie, HM;Rainey, GJA;Young, JAT
通讯作者：
Young, JAT
影响因子：
2.9
作者：
Miller, CJ;Elliott, JL;Collier, RJ
通讯作者：
Collier, RJ
影响因子：
2.9
作者：
Nassi, S;Collier, RJ;Finkelstein, A
通讯作者：
Finkelstein, A
DOI：
10.1073/pnas.0505865102
发表时间：
2005-09-13
影响因子：
11.1
作者：
Rainey, GJA;Wigelsworth, DJ;Young, JAT
通讯作者：
Young, JAT